Dr. Nicole Vu, Scientific Director, ARL
Pharmaceutical ingredients are controlled by cGMP regulations. Users of pharmaceutical materials should be informed regarding when the material can be re-tested for continued use.
ICH Q1A(R2)/FDA Definition:
Expiration date: The date placed on the container/labels of an API designating the time during which the API is expected to remain within established shelf-life specifications if stored under defined conditions and after which it should not be used.
Retest date: The date when a material should be reexamined to ensure that it is still suitable for use.
Retest period: The period of time during which the drug substance is expected to remain within its specification and, therefore, can be used in the manufacture of a given drug product, provided that the drug substance has been stored under the defined conditions. After this period, a batch of drug substance destined for use in the manufacture of a drug product should be retested for compliance with the specification and then used immediately. A batch of drug substance can be retested multiple times and a different portion of the batch used after each retest, as long as it continues to comply with the specification. For biotechnological/biological substances known to be labile, it is more appropriate to establish a shelf-life than a retest period. The same may be true for certain antibiotics.
Additional information (ICH Q7A: Good Manufacturing Practice Guide For Active Pharmaceutical Ingredients)
- An API expiry or retest date should be based on an evaluation of data derived from stability studies. Common practice is to use a retest date, not an expiration date (Section 11.6). Some very labile materials such as antibiotics and biotech materials may be required to be labeled with an expiration date. The retest date or the expiration date is listed either on the container or on the COA.
- If the API material has an assigned expiration date: User of the API material cannot extend the manufacturer's expiration date by means of re-testing.
- If the API is labeled with a retest date: The API material can be re-tested, and if retest results are in compliance with the material specification for critical attributes, such as content and purity (chemical & microbiological), the batch may be used immediately. Test results must be obtained with pharmacopeial procedures or stability indicating methods, using primary reference standard. Use immediately is not defined by the FDA. Common practice in the industry is to use within 30 days of the retest date.
- Under current rule, a new date for retesting beyond 30 days of immediate use should be based on current retest results and supporting stability data. Successive retest periods may not be longer than the original retest period assigned by the manufacturer of the API.
- Section 19.8: Expiry and retest dating as defined in Section 11.6 applies to existing APIs used in clinical trials (i.e., established APIs). New APIs in the early stage of clinical trials (non-established APIs) are not required to have an expiration date nor a retest period.